Gonadal steroids are major neuroregulators and presumably underlie gender-related differences (sexual dimorphisms) in brain structure and function. We have studied reproductive endocrine-related mood disorders as well as developed endocrine models for these disorders in order to characterize the role of gonadal steroids in affective disturbance. In the past year, our major findings are as follows: 1) estrogen or progesterone precipitates return of premenstrual syndrome symptoms in women successfully treated by medication (leuprolide) induced hypogonadism but not in women lacking a history of premenstrual syndrome. Premenstrual syndrome, therefore, represents an abnormal response to normal hormone levels. 2) Estrogen and, to a greater extent, progesterone enhance the cortisol and ACTH responses to exercise-induced stress relative to leuprolide-induced hypogonadism, thus potentially contributing to sexual dimorphisms or menstrual cycle phase-related differences in stress response. 3) Euthymic women with a history of postpartum depression appear differentially sensitive to changes in gonadal steroid levels, as they, but not controls, experience significant depression during blinded withdrawal from high dose gonadal steroid administration. These observations, then, demonstrate not only the marked impact of gonadal steroids on neuroendocrine function and behavior in humans, but demonstrate as well that women with histories of reproductive endocrine-related mood disorders display an abnormal response to normal levels of gonadal steroids.